褪黑素通過lncRNA H19-miRNA-29c對糖尿病大鼠心肌細胞凋亡的影響

褪黑素通過lncRNAH19-miRNA-29c對糖尿病大鼠心肌細胞凋亡的影響摘要：糖尿病是一種常見疾病，可引起心肌細胞凋亡，導致心血管并發(fā)癥的發(fā)展。褪黑素作為神經(jīng)內(nèi)分泌調(diào)節(jié)劑和抗氧化劑，對于糖尿病心肌細胞凋亡的調(diào)節(jié)具有潛在的治療作用。然而，褪黑素對心肌細胞凋亡的分子機制仍不清楚。本研究旨在探討褪黑素作用的分子基礎(chǔ)，主要研究H19/miRNA-29c通路，探究其在褪黑素調(diào)控心肌細胞凋亡中的作用。通過建立糖尿病大鼠模型，采用體外和體內(nèi)實驗方法研究褪黑素對心肌細胞凋亡的影響和機制。結(jié)果顯示，褪黑素可抑制心肌細胞凋亡，并且通過下調(diào)H19表達，上調(diào)miRNA-29c表達來實現(xiàn)對糖尿病大鼠心肌細胞凋亡的抑制。本研究結(jié)果表明褪黑素在調(diào)控糖尿病心肌細胞凋亡中起到重要作用，H19/miRNA-29c通路可能是褪黑素調(diào)控心肌細胞凋亡的分子機制之一。

關(guān)鍵詞：褪黑素；心肌細胞凋亡；H19；miRNA-29c；糖尿病大鼠

Introduction：糖尿病是一種常見代謝性疾病，其患者發(fā)生心血管并發(fā)癥的風險較高。心肌細胞凋亡是糖尿病心臟病變的重要機制之一。褪黑素是一種神經(jīng)內(nèi)分泌調(diào)節(jié)劑，已被證明具有保護心肌細胞免受氧化損傷的潛在作用。然而，褪黑素對心肌細胞凋亡的分子機制仍不清楚。

Materialsandmethods：采用糖尿病大鼠模型，分別用體外和體內(nèi)實驗方法研究褪黑素對心肌細胞凋亡的影響和機制。使用細胞計數(shù)法和流式細胞術(shù)檢測心肌細胞凋亡率；采用Westernblot和RT-PCR檢測miRNA-29c和H19的表達水平，進一步研究H19/miRNA-29c通路的作用。

Results：褪黑素處理后，心肌細胞凋亡率顯著下降，miRNA-29c表達升高，而H19表達下降。采用H19干擾RNA干預，發(fā)現(xiàn)其可完全抑制褪黑素對miRNA-29c表達的上調(diào)和心肌細胞凋亡率的下降。

Conclusion：本研究表明了褪黑素作為一種神經(jīng)內(nèi)分泌調(diào)節(jié)劑和抗氧化劑，可以通過調(diào)節(jié)H19/miRNA-29c通路來抑制心肌細胞凋亡，具有潛在的治療作用，為糖尿病心臟病變的防治提供了新的思路Discussion:

Diabetesisacommonmetabolicdiseasethatincreasestheriskofcardiovascularcomplicationsinpatients.Oneoftheimportantmechanismsofdiabeticcardiomyopathyismyocardialcellapoptosis.Melatoninisaneuroendocrinemodulatorthathasbeenshowntohavepotentialinprotectingmyocardialcellsfromoxidativedamage.However,themolecularmechanismofmelatoninonmyocardialcellapoptosisisstillunclear.

Inthisstudy,weinvestigatedtheeffectandmechanismofmelatoninonmyocardialcellapoptosisusingbothinvitroandinvivoexperimentsinadiabeticratmodel.Ourresultsshowedthatmelatonintreatmentsignificantlyreducedmyocardialcellapoptosisrate,increasedtheexpressionofmiRNA-29c,anddecreasedtheexpressionofH19.

RecentstudieshaveshownthatH19isanimportantlongnon-codingRNAthatregulatesgeneexpressionandplaysaroleinmyocardialcellapoptosis.miRNA-29cisamemberofthemiRNAfamilythatregulatescellapoptosisbytargetingmultiplegenes.OurresultssuggestthattheH19/miRNA-29cpathwaymaybeinvolvedintheregulationofmyocardialcellapoptosisbymelatonin.

Moreover,ourstudyfoundthatsilencingH19couldcompletelyinhibittheupregulationofmiRNA-29cexpressionandthedecreaseinmyocardialcellapoptosisrateinducedbymelatonin.TheseresultsindicatethatmelatonincaninhibitmyocardialcellapoptosisthroughtheH19/miRNA-29cpathway.

Inconclusion,ourstudysuggeststhatmelatonin,asaneuroendocrinemodulatorandantioxidant,mayhavepotentialtherapeuticeffectsondiabeticcardiomyopathybyregulatingtheH19/miRNA-29cpathway.Ourfindingsprovidenewinsightsintothepreventionandtreatmentofdiabeticheartdisease.However,furtherstudiesareneededtoclarifytheunderlyingmechanismandexploretheclinicalimplicationsofourfindingsFurtherstudiesareneededtoevaluatetheoptimaldoseandadministrationofmelatonininthetreatmentofdiabeticcardiomyopathy.Inaddition,clinicaltrialsarenecessarytovalidatetheeffectivenessandsafetyofusingmelatoninasatherapeuticagentfordiabeticheartdisease.

FuturestudiesshouldalsoinvestigatetheroleoftheH19/miRNA-29cpathwayinothercardiovasculardiseasesandelucidatethemolecularmechanismofhowmelatoninregulatesthispathway.Itwouldbeinterestingtoexplorewhethermelatonincanalsoregulateothernon-codingRNApathwaysthatareinvolvedincardiovasculardisease,suchaslongnon-codingRNAorcircularRNApathways.

Moreover,theeffectsofmelatoninonotheraspectsofdiabeticcardiomyopathy,suchasinflammation,fibrosis,andoxidativestress,shouldbeinvestigated.Thesestudiesmayprovideamorecomprehensiveunderstandingofthetherapeuticpotentialofmelatoninfordiabeticheartdisease.

Insummary,ourstudyhighlightsthepotentialtherapeuticeffectsofmelatoninondiabeticcardiomyopathythroughtheregulationoftheH19/miRNA-29cpathway.Asasafeandwell-toleratedagent,melatoninmayprovideanoveltherapeuticstrategyforthepreventionandtreatmentofdiabeticheartdisease.However,furtherstudiesareneededtofullyelucidatetheunderlyingmechanismsandevaluatetheclinicalimplicationsofthesefindingsDespiteadvancesinclinicalmanagement,diabeticcardiomyopathyremainsamajorcauseofmorbidityandmortalityamongdiabeticpatients.Assuch,thereisacriticalneedforsafeandeffectivetherapiesthatcanpreventordelaythedevelopmentofthiscondition.Melatoninhasemergedasapromisingcandidateduetoitsnumerousbeneficialeffectsonthecardiovascularsystem,aswellasitssafetyandlowcost.

Melatoninfunctionsasapowerfulantioxidantandanti-inflammatoryagent,whichmayhelptoprotectagainsttheoxidativeandinflammatorydamagethatcontributestothepathogenesisofdiabeticcardiomyopathy.Furthermore,melatoninhasbeenshowntomodulatetheexpressionofkeygenesandmiRNAsinvolvedincardiacfunctionandmetabolism,whichcouldinturnimprovecardiacfunctionandpreventdiseaseprogression.

Severalanimalstudieshaveprovidedevidenceoftheefficacyofmelatoninindiabeticcardiomyopathy.Forexample,inaratmodelofstreptozotocin-induceddiabetes,melatonintreatmentwasfoundtoimprovecardiacfunction,reduceoxidativestressandinflammation,andmitigatefibrosisandapoptosisintheheart.Similarly,inamousemodeloftype2diabetes,melatoninsupplementationwasfoundtoattenuatecardiacdysfunctionandfibrosis,aswellasimproveglucosemetabolismandinsulinsensitivity.

Whiletheresultsofanimalstudiesarepromising,furtherstudiesareneededtodeterminetheclinicalefficacyofmelatonininthetreatmentofdiabeticcardiomyopathy.Clinicaltrialsarecurrentlyunderwaytoevaluatethesafetyandefficacyofmelaton